Pathogenesis of Acute Coronary Syndrome part 2

         Recent pathogenesis explains acute coronary syndrome, acute coronary syndrome (ACS) is caused by obstruction and thrombotic occlusion of the coronary arteries, which is caused by a vulnerable atherosclerotic plaque erosion, fissure, or rupture. The main cause of acute coronary syndrome triggered by erosion, fissure, or rupture of atherosclerotic plaques is due to the presence of the condition of unstable atherosclerotic plaques (vulnerable atherosclerotic plaques) with characteristics; substantial lipid core, thin fibrous cups, and the plaque shoulder (shoulder region of the plague) full the activity of inflammatory cells such as T lymphocytes and others (Figure A). Thick plaque that can be seen with the percentage of narrowing of the coronary arteries on coronary angiography examination does not mean anything as long as the plaque in stable condition. In other words, the risk of plaque rupture in atherosclerosis is not determined by the amount of plaque (degree of constriction) but by vulnerability (vulnerability) plaques.

Figure A. Characteristics of vulnerable plaques / unstable (vulnerable)

         Erosion, fissures, or atherosclerotic plaque rupture (which already exist in the walls of the coronary arteries) secrete vasoactive substances (collagen, lipid core, macrophages and tissue factor) into the bloodstream, stimulating aggregation and adhesion of platelets and fibrin formation, the process of forming a thrombus or thrombosis . Formed thrombus can lead to total or subtotal coronary occlusion. Severe coronary occlusion caused by erosion or rupture of atherosclerotic plaques that relatively little will cause Unstable Angina and not to cause tissue death. Thrombus usually transient / unstable and cause temporary occlusion lasting between 10-20 minutes (Table 1).

Table 1

        When occlusion causes tissue death, but can be overcome by collateral or rapid lysis of thrombus (spontaneously or by the action of thrombolytic) will arise NSTEMI (not all layers of myocardial damage). Thrombus occurring more persistent and lasts for more than 1 hour. When occlusion dikompesasi settled and not by the overall layer collateral myocardial necrosis (Q-wave infarction), or also known as STEMI. Thrombus formed is fixed and persistent causes myocardial perfusion stopped abruptly lasting more than 1 hour and causing transmural myocardial necrosis.

         Now more and more clearly believed that thrombosis is the basic mechanism of the acute coronary syndrome, thrombosis in coronary arteries is mainly caused by the rupture of vulnerable atherosclerotic plaques due to fibrous protective cups that had become thin, cracked and broken. Fibrous layer of the cups is not a static, but always having remodeling due to metabolic activities, endothelial dysfunction, the role of inflammatory cells, extracellular matrix interference or extra-cellular matrix (ECM) by the action of matrix metallo proteinases (MMPs), which inhibit the formation of collagen and activity of inflammatory cytokines.

     Recent developments explained and established that inflammatory processes crucial role in the biological process of photograph-acute coronary syndrome, where plaque vulnerability is determined by the inflammatory process. Inflammation can be local (on the plaque itself) and can be systemic. Inflammation can also interfere with homeostatic balance. In the state of inflammation are elevated concentrations of fibrinogen and plasminogen activator inhibitor in the circulation. Inflammation can also cause vasospasm of the blood vessels due to impaired blood flow.

     Vasoconstriction of the coronary arteries also had a role in the pathogenesis of ACS. Vasoconstriction occurs in response to mild endothelial dysfunction near the lesion or in response to a disruption of the plaque of the lesion itself. Endothelial function regulate vascular tone by releasing relaxing factors are nitric oxide (NO) is known as the endothelium Derived Relaxing Factor (EDRF), prostacyclin, and contraction factors such as endothelin-1, thromboxane A2, prostaglandin H2. On endothelial dysfunction, the contraction factor is more dominant than the relaxation factor. On plaque disruption had occurred vasocontriction dependent platelet mediated by serotonin and thromboxane A2, and thrombin dependent vasoconstriction may be due to direct interaction between these substances by vascular smooth muscle cells.